Trial Information

CYP2D6 Genotyping by AmpliChipTM CYP450 for Tamoxifen-Treated Breast Cancer Patients

Tamoxifen, the first-line drug for preventing breast cancer relapse, is typically prescribed
for a 5-year follow-up period after diagnosis and primary treatment of estrogen
receptor-positive breast cancer. Recent studies show that tamoxifen is only a pro-drug,
while its major active metabolite, endoxifen, is formed in vitro by the liver enzyme CYP2D6.
Preliminary observations from the US and Italy have suggested that tamoxifen is less
efficacious for cancer relapse prevention in patients with deficient CYP2D6 activities. The
FDA is currently reviewing the new data and is likely to modify the tamoxifen label
accordingly. It was suggested that an aromatase inhibitor drug such as letrozole might be
more beneficial for these patients.

The proposed study would retrospectively test CYP2D6 genotypes in 200 - 300 estrogen
receptor (ER) positive breast cancer patients who are treated with tamoxifen
post-operatively. Blood collected with informed consent would be used for examining the
patients CYP2D6 genotype, and identifying those who are CYP2D6 poor metabolizers
(CYP2D6*4/*4 genotype), and for measurement of endoxifen blood level in those women who are
on the drug.

AmpliChipTM CYP450 is a microarray chip which contains millions of tiny DNA molecules,
providing comprehensive coverage of gene variations that play a role in the metabolism of
approximately 25% of all prescription drugs. The AmpliChipTM CYP450 test is intended to be
an aid for physicians in individualizing treatment doses for patients receiving therapeutics
metabolized through these enzymes.

The clinical data collected would examine if these individuals, as well as those treated
with CYP2D6 inhibiting drugs such as paroxetine and fluoxetine, have higher cancer relapse
rates.

The study, combined with similar findings from other countries, and possibly integrated
later on with an international network study, would be imperative for modifying treatment
recommendations for breast cancer therapy. Specifically, if the US and Italian findings are
confirmed, it might be advisable to switch the 5-year follow-up treatment for breast cancer
patients with ER positive primary tumors who are CYP2D6 poor metabolizers from tamoxifen to
an aromatase inhibitor drug such as letrozole.